The overall objective of this proposal is to develop methods for synthesis of biologically active protein-protein conjugates containing an enzyme and a cell surface receptor-binding protein for use as probes to study the mechanism of cell surface receptor-mediated protein transports. The proteins to be studied will involve plant and bacterial toxins, polypeptide hormones, lysosomal enzymes, desialylated glycoproteins and lipoproteins. Once a conjugate is synthesized its uptake through the putative receptor-binding protein-receptor interaction process and its express of biological activity intracellularly will be studied with receptor cell cultures. The information obtained from these studies will be useful for determining whether or not it is possible to utilize various receptor-mediated protein transport systems for introducing lysosomal enzymes into deficient cells for enzyme replacement therapy and toxin active fragment for cancer chemotherapy.